Despite aggressive modern treatments, Streptococcus pyogenes-associated toxic shock syndrome (Strep-TSS) continues to be a growing concern for the health care industry. Along with necrotizing fasciitis, patients that develop these infections may also develop a unique form of cardiac depression referred to as Strep-TSS associated cardiomyopathy which is characterized by poor cardiac output and reduced ejection fraction. At present, the mechanism surrounding this form of cardiomyopathy is still unknown. The receptor for advanced glycation end-products (RAGE) has been implicated in several other inflammatory diseases and thus, could play a major role in the symptoms associated with Strep-TSS associated cardiomyopathy. The objective of my research was to determine if the RAGE pathway is involved in the pathogenesis of Strep-TSS associated cardiomyopathy. This was accomplished by assessing RAGE ligand expression in mouse cardiomyocytes and heart tissue after challenge with Streptococcus pyogenes. Results indicated that RAGE ligands S100A9 and S100A8 are upregulated in vivo after challenge with Group A Strep (GAS) while in vitro studies showed upregulated transcript of S100A8 but not S100A9 after GAS challenge. These results suggest that engagement of RAGE by its ligands may be responsible for the unique type of cardiomyopathy seen in patients with Strep-TSS. Faculty Sponsor: Ann Koga This project was funded by a NIH-INBRE research grant.

Streptococcus Pyogenes and Associated Cardiomyopathy